Ripasudil的新合成工艺
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摘要
4-氟异喹啉-5-磺酰氯与(S)-2-氨基-N-(叔丁氧羰基)-N-(3-叔丁基二甲基硅烷氧基丙基)丙胺发生偶联反应,经TBAF脱去羟基保护后通过Mitsunobu反应自身环合,最后脱氨基保护得到青光眼治疗药物ripasudil,总收率31.3%。
Ripasudil was synthesized from 4-fluoroisoquinoline-5-sulfonyl chloride by coupling reaction with(S)-2-amino-N-(tert-butoxycarbonyl)-N-(3-tert-butyldimethylsilyloxypropyl)propylamine,then subjected to hydroxy deprotection with TBAF and then Mitsunobu reaction,followed by Boc deprotection with an overall yield of about 31.3%.
Ripasudil was synthesized from 4-fluoroisoquinoline-5-sulfonyl chloride by coupling reaction with(S)-2-amino-N-(tert-butoxycarbonyl)-N-(3-tert-butyldimethylsilyloxypropyl)propylamine,then subjected to hydroxy deprotection with TBAF and then Mitsunobu reaction,followed by Boc deprotection with an overall yield of about 31.3%.
引文
[1]五味宣明,扇谷忠明,涩谷公幸,异喹啉衍生物或其盐的新制造方法:中国,103068818A[P].2013-04-24.
[2]Garnock-Jones KP.Ripasudil:First global approval[J].Drugs,2014,74(18):2211-2215.
[3]Tanihara H,Inoue T,Yamamoto T,et al.Intra-ocular pressurelowering effects of a Rho kinase inhibitor,ripasudil(K-115),over 24 hours in primary open-angle glaucoma and ocular hypertension:a randomized,open-label,crossover study[J].Acta Ophthalmologica,2015,93(4):254-260.
[4]Gomi N,Ohgiya T,Shibuya K,et al.A practical synthesis of novel Rho-kinase inhibitor,(S)-4-fluoro-5-(2-methyl-l,4-diazepan-1-ylsulfonyl)isoquinoline[J].Heterocycles,2011,83(8):1771-1781.
[5]大岛武,日高弘义,白土正三,等(S)-(-)-1-(4-氟异喹啉-5-基)磺酰基-2-甲基-1,4-高哌嗪盐酸盐-二水合物:中国,101068806A[P].2007-11-07.
[6]Sumi K,Inoue Y,Nishio M,et al.IOP-lowering effect of isoquinoline-5-sulfonamide compounds in ocular normotensive monkeys[J].Bioorg Med Chem Lett,2014,24(3):831-834.
[7]Gomi N,Higashimurayama S,Ohgiya T,et al.Novel production method for isoquinoline derivatives and salts thereof:US,2013 0144054[P].2013-06-06.
[2]Garnock-Jones KP.Ripasudil:First global approval[J].Drugs,2014,74(18):2211-2215.
[3]Tanihara H,Inoue T,Yamamoto T,et al.Intra-ocular pressurelowering effects of a Rho kinase inhibitor,ripasudil(K-115),over 24 hours in primary open-angle glaucoma and ocular hypertension:a randomized,open-label,crossover study[J].Acta Ophthalmologica,2015,93(4):254-260.
[4]Gomi N,Ohgiya T,Shibuya K,et al.A practical synthesis of novel Rho-kinase inhibitor,(S)-4-fluoro-5-(2-methyl-l,4-diazepan-1-ylsulfonyl)isoquinoline[J].Heterocycles,2011,83(8):1771-1781.
[5]大岛武,日高弘义,白土正三,等(S)-(-)-1-(4-氟异喹啉-5-基)磺酰基-2-甲基-1,4-高哌嗪盐酸盐-二水合物:中国,101068806A[P].2007-11-07.
[6]Sumi K,Inoue Y,Nishio M,et al.IOP-lowering effect of isoquinoline-5-sulfonamide compounds in ocular normotensive monkeys[J].Bioorg Med Chem Lett,2014,24(3):831-834.
[7]Gomi N,Higashimurayama S,Ohgiya T,et al.Novel production method for isoquinoline derivatives and salts thereof:US,2013 0144054[P].2013-06-06.